Substantial data has been accumalted from the mouse epidermal carcinogenesis model to strongly suggest that the induction of ODC is a specific and essential event in the 12-0 tetradecanoylphorbol-13-acetate (TPA) promotion of skin tumors. Recent evidence by Olson and Russell, using a multi-stage hepatocarcinogenesis model, has provided evidence that suggests the prolonged activation of cyclic AMP-dependent protein kinase (cA-PK), elevation of ODC and increased spemidine levels are coupled to the hyperplastic liver nodule formation. This project will further test the hypothesis that prolonged induction of ornithine decarboxylase (ODC) and the ensuing increased polyamine levels are a necessary event for the development of preneoplastic (hyperplastic) nodules and the eventual formatin of malignant neoplasms. Determination of the significance of the ovserved ODC induction will be aided by the use of two pharmacological agents: DFMO, irreversibel inhibitor of ODC, or a retinoid will be administered to rats subjected to the hepatocarcinogenesis regimen. Tissue samples from liver of rats subjected to the above treatments will be monitored for ODC activity, SAM-DC activity, polyamines and cA-PK isozymes. These results will be contrasted with the development and progression of hyperplastic nodules. This information will provide further useful information about the proposed significant events in hepatocarcinogenesis. This detailed knowledge may possibly be directly applicable to the development of regimens for the prevention and therapy of human cancer.